Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.

<h4>Background</h4>Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus that causes acute febrile illness, meningitis, and meningoencephalitis, primarily in North American adults. Currently, there are no available vaccines or specific treatments against JCV infections.<h4&...

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Autores principales:	Hirofumi Kato, Mutsuyo Takayama-Ito, Masaaki Satoh, Madoka Kawahara, Satoshi Kitaura, Tomoki Yoshikawa, Shuetsu Fukushi, Nozomi Nakajima, Takashi Komeno, Yousuke Furuta, Masayuki Saijo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/41c4f1daeb3344f18339d74e13a708c1
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spelling	oai:doaj.org-article:41c4f1daeb3344f18339d74e13a708c12021-12-02T20:23:48ZFavipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.1935-27271935-273510.1371/journal.pntd.0009553https://doaj.org/article/41c4f1daeb3344f18339d74e13a708c12021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009553https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus that causes acute febrile illness, meningitis, and meningoencephalitis, primarily in North American adults. Currently, there are no available vaccines or specific treatments against JCV infections.<h4>Methodology/principal findings</h4>The antiviral efficacy of favipiravir (FPV) against JCV infection was evaluated in vitro and in vivo in comparison with that of ribavirin (RBV) and 2'-fluoro-2'-deoxycytidine (2'-FdC). The in vitro inhibitory effect of these drugs on JCV replication was evaluated in Vero and Neuro-2a (N2A) cells. The efficacy of FPV in the treatment of JCV infection in vivo was evaluated in C57BL/6J mice inoculated intracerebrally with JCV, as per the survival, viral titers in the brain, and viral RNA load in the blood. The 90% inhibitory concentrations (IC90) of FPV, RBV, and 2'-FdC were 41.0, 61.8, and 13.6 μM in Vero cells and 20.7, 25.8, and 8.8 μM in N2A cells, respectively. All mice infected with 1.0×104 TCID50 died or were sacrificed within 10 days post-infection (dpi) without treatment. However, mice treated with FPV for 5 days [initiated either 2 days prior to infection (-2 dpi-2 dpi) or on the day of infection (0 dpi-4 dpi)] survived significantly longer than control mice, administered with PBS (p = 0.025 and 0.011, respectively). Moreover, at 1 and 3 dpi, the virus titers in the brain were significantly lower in FPV-treated mice (0 dpi-4 dpi) versus PBS-treated mice (p = 0.002 for both 1 and 3 dpi).<h4>Conclusions/significance</h4>Although the intracerebral inoculation route is thought to be a challenging way to evaluate drug efficacy, FPV inhibits the in vitro replication of JCV and prolongs the survival of mice intracerebrally inoculated with JCV. These results will enable the development of a specific antiviral treatment against JCV infections and establishment of an effective animal model.Hirofumi KatoMutsuyo Takayama-ItoMasaaki SatohMadoka KawaharaSatoshi KitauraTomoki YoshikawaShuetsu FukushiNozomi NakajimaTakashi KomenoYousuke FurutaMasayuki SaijoPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 7, p e0009553 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Hirofumi Kato Mutsuyo Takayama-Ito Masaaki Satoh Madoka Kawahara Satoshi Kitaura Tomoki Yoshikawa Shuetsu Fukushi Nozomi Nakajima Takashi Komeno Yousuke Furuta Masayuki Saijo Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.
description	<h4>Background</h4>Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus that causes acute febrile illness, meningitis, and meningoencephalitis, primarily in North American adults. Currently, there are no available vaccines or specific treatments against JCV infections.<h4>Methodology/principal findings</h4>The antiviral efficacy of favipiravir (FPV) against JCV infection was evaluated in vitro and in vivo in comparison with that of ribavirin (RBV) and 2'-fluoro-2'-deoxycytidine (2'-FdC). The in vitro inhibitory effect of these drugs on JCV replication was evaluated in Vero and Neuro-2a (N2A) cells. The efficacy of FPV in the treatment of JCV infection in vivo was evaluated in C57BL/6J mice inoculated intracerebrally with JCV, as per the survival, viral titers in the brain, and viral RNA load in the blood. The 90% inhibitory concentrations (IC90) of FPV, RBV, and 2'-FdC were 41.0, 61.8, and 13.6 μM in Vero cells and 20.7, 25.8, and 8.8 μM in N2A cells, respectively. All mice infected with 1.0×104 TCID50 died or were sacrificed within 10 days post-infection (dpi) without treatment. However, mice treated with FPV for 5 days [initiated either 2 days prior to infection (-2 dpi-2 dpi) or on the day of infection (0 dpi-4 dpi)] survived significantly longer than control mice, administered with PBS (p = 0.025 and 0.011, respectively). Moreover, at 1 and 3 dpi, the virus titers in the brain were significantly lower in FPV-treated mice (0 dpi-4 dpi) versus PBS-treated mice (p = 0.002 for both 1 and 3 dpi).<h4>Conclusions/significance</h4>Although the intracerebral inoculation route is thought to be a challenging way to evaluate drug efficacy, FPV inhibits the in vitro replication of JCV and prolongs the survival of mice intracerebrally inoculated with JCV. These results will enable the development of a specific antiviral treatment against JCV infections and establishment of an effective animal model.
format	article
author	Hirofumi Kato Mutsuyo Takayama-Ito Masaaki Satoh Madoka Kawahara Satoshi Kitaura Tomoki Yoshikawa Shuetsu Fukushi Nozomi Nakajima Takashi Komeno Yousuke Furuta Masayuki Saijo
author_facet	Hirofumi Kato Mutsuyo Takayama-Ito Masaaki Satoh Madoka Kawahara Satoshi Kitaura Tomoki Yoshikawa Shuetsu Fukushi Nozomi Nakajima Takashi Komeno Yousuke Furuta Masayuki Saijo
author_sort	Hirofumi Kato
title	Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.
title_short	Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.
title_full	Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.
title_fullStr	Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.
title_full_unstemmed	Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.
title_sort	favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with jamestown canyon virus.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/41c4f1daeb3344f18339d74e13a708c1
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Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.

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